Journal of Antimicrobial Chemotherapy最新文献

{"title":"Prediction of teicoplanin plasma concentration in critically ill patients: a combination of machine learning and population pharmacokinetics.","authors":"Pan Ma, Shenglan Shang, Ruixiang Liu, Yuzhu Dong, Jiangfan Wu, Wenrui Gu, Mengchen Yu, Jing Liu, Ying Li, Yongchuan Chen","doi":"10.1093/jac/dkae292","DOIUrl":"10.1093/jac/dkae292","url":null,"abstract":"<p><strong>Background: </strong>Teicoplanin has been widely used in patients with infections caused by Staphylococcus aureus, especially for critically ill patients. The pharmacokinetics (PK) of teicoplanin vary between individuals and within the same individual. We aim to establish a prediction model via a combination of machine learning and population PK (PPK) to support personalized medication decisions for critically ill patients.</p><p><strong>Methods: </strong>A retrospective study was performed incorporating 33 variables, including PPK parameters (clearance and volume of distribution). Multiple algorithms and Shapley additive explanations were employed for feature selection of variables to determine the strongest driving factors.</p><p><strong>Results: </strong>The performance of each algorithm with PPK parameters was superior to that without PPK parameters. The composition of support vector regression, categorical boosting and a backpropagation neural network (7:2:1) with the highest R2 (0.809) was determined as the final ensemble model. The model included 15 variables after feature selection, of which the predictive performance was superior to that of models considering all variables or using only PPK. The R2, mean absolute error, mean squared error, absolute accuracy (±5 mg/L) and relative accuracy (±30%) of external validation were 0.649, 3.913, 28.347, 76.12% and 76.12%, respectively.</p><p><strong>Conclusions: </strong>Our study offers a non-invasive, fast and cost-effective prediction model of teicoplanin plasma concentration in critically ill patients. The model serves as a fundamental tool for clinicians to determine the effective plasma concentration range of teicoplanin and formulate individualized dosing regimens accordingly.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2815-2827"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of erm(B) in a clinical Campylobacter jejuni isolate from China.","authors":"Fen Gao, Jiayuan Luo, Min Chen","doi":"10.1093/jac/dkae294","DOIUrl":"10.1093/jac/dkae294","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"3043-3045"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study.","authors":"Antonio Vena, Michela Schenone, Silvia Corcione, Maddalena Giannella, Renato Pascale, Daniele Roberto Giacobbe, Marco Muccio, Simone Mornese Pinna, Bianca Pari, Francesca Giovannenze, Nicholas Geremia, Malgorzata Mikulska, Eleonora Taddei, Flavio Sangiorgi, Davide Fiore Bavaro, Vincenzo Scaglione, Veronica Vassia, Marco Merli, Michele Bartoletti, Pierluigi Viale, Francesco Giuseppe De Rosa, Matteo Bassetti","doi":"10.1093/jac/dkae296","DOIUrl":"10.1093/jac/dkae296","url":null,"abstract":"<p><strong>Objectives: </strong>To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI).</p><p><strong>Methods: </strong>This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021-2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses.</p><p><strong>Results: </strong>Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12-0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25-2.14; P = 0.568).</p><p><strong>Conclusions: </strong>AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2846-2853"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenacapavir to prevent HIV infection: current prices versus estimated costs of production.","authors":"Andrew Hill, Jacob Levi, Cassandra Fairhead, Victoria Pilkington, Junzheng Wang, Madison Johnson, Jevon Layne, David Roberts, Joseph Fortunak","doi":"10.1093/jac/dkae305","DOIUrl":"10.1093/jac/dkae305","url":null,"abstract":"<p><strong>Background: </strong>Despite improvements in treatment and oral pre-exposure prophylaxis (PrEP) access, 1.3 million people acquired HIV in 2022. Six-monthly lenacapavir PrEP could benefit tens of millions of people at high risk of infection. However, prices are currently up to $44 819 per person per year (pppy).</p><p><strong>Objectives: </strong>We projected minimum lenacapavir pricing based on generic mass production and a Cost-Plus (Cost+) model.</p><p><strong>Methods: </strong>Current active pharmaceutical ingredient (API) and key starting materials (KSMs) costs were obtained from export databases. The routes of synthesis (ROS) were analysed to project a cost of goods (COGs). Formulation, vials and profit margin costs were included using standardized algorithms and Cost+ pricing. We estimated prices with scale-up to supply 1 million then 10 million treatment-years, comparing this with national list prices.</p><p><strong>Results: </strong>The lenacapavir API is currently exported from India for $64 480/kg on 1 kg scale. Based on the ROS and KSMs, API COGs of $25 000/kg and $10 000/kg are achievable for a committed demand of 1 million (2 million tonnes/annum of API) and 10 million treatment-years, respectively. Including formulation steps, injectable lenacapavir could be mass produced for approximately $94 pppy for 1 million and $41 for 10 million treatment-years, if voluntary licences are in place and competition between generic suppliers substantially improves. Greater scale-up with improvements in manufacturers' ROS could reduce prices further. Currently lenacapavir costs $25 395-44 819 pppy.</p><p><strong>Conclusions: </strong>Lenacapavir could be mass produced for <$100 pppy at launch. Voluntary licensing and multiple suppliers are required to achieve these low prices. This mechanism is already in place for other antiretrovirals. To date, Gilead has not agreed lenacapavir voluntary licences with the Medicines Patent Pool.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2906-2915"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of oral fosfomycin calcium in healthy women.","authors":"Arantxa Isla, Ana Alarcia-Lacalle, María Ángeles Solinís, Ana Del Pozo-Rodríguez, Zuriñe Abajo, María Cabero, Andrés Canut-Blasco, Alicia Rodríguez-Gascón","doi":"10.1093/jac/dkae295","DOIUrl":"10.1093/jac/dkae295","url":null,"abstract":"<p><strong>Background: </strong>Fosfomycin is an antibiotic extensively used to treat uncomplicated urinary tract infections in women, and it is available in different salts and formulations. The European Medicines Agency (EMA) recommends further studies to characterize the pharmacokinetics of fosfomycin calcium for oral administration and to justify its dosage recommendation.</p><p><strong>Objectives: </strong>A population pharmacokinetic model of fosfomycin calcium was developed after oral administration to healthy women.</p><p><strong>Methods: </strong>A clinical trial (a randomized, open-label, bioavailability study of single and multiple doses of 1000 mg capsules, single dose of 500 mg capsule and single dose of 250 mg/5 mL suspension of oral fosfomycin calcium under fasted conditions in healthy women volunteers, Code: PD7522.22, EudraCT: 2020-001664-28) was carried out at the Clinical Trial Unit, Araba University Hospital (Vitoria-Gasteiz, Spain). Twenty-four healthy women were included in the study, and plasma samples were collected at different times over a period of 24 h. The concentration-time data of fosfomycin in plasma were modelled by a population approach using a nonlinear mixed-effects modelling implemented by NONMEM 7.4 (ICON Clinical Research LLC, North Wales, PA, USA).</p><p><strong>Results: </strong>The pharmacokinetics of fosfomycin was best described by a two-compartment model. Creatinine clearance and body weight were identified as covariates for fosfomycin clearance and volume of distribution, respectively.</p><p><strong>Conclusions: </strong>This study provides relevant information on the pharmacokinetic profile of fosfomycin in women after oral administration as calcium salt. This population model may be very useful for establishing dosage recommendations of fosfomycin calcium to treat urinary tract infections in women.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2837-2845"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activity of antibiotics against Burkholderia cepacia complex in artificial sputum medium.","authors":"Anusha Shukla, Shade Rodriguez, Thea Brennan-Krohn","doi":"10.1093/jac/dkae299","DOIUrl":"10.1093/jac/dkae299","url":null,"abstract":"<p><strong>Background: </strong>Burkholderia cepacia complex (Bcc) is a collection of intrinsically drug-resistant Gram-negative bacteria that cause life-threatening disease in people with cystic fibrosis (CF). Standard antimicrobial susceptibility testing methods have poor predictive value for clinical outcomes in Bcc infections, probably due in part to differences between in vitro testing conditions and the environment in which Bcc grow in the lungs of people with CF.</p><p><strong>Objectives: </strong>To compare the activity of commonly used antibiotics under standard in vitro testing conditions with activity in conditions mimicking those found in vivo.</p><p><strong>Methods: </strong>Two Bcc strains were grown alone and with six different antibiotics (minocycline, ceftazidime, meropenem, tobramycin, levofloxacin, trimethoprim-sulfamethoxazole) in two different media: standard cation-adjusted Mueller-Hinton broth and an artificial sputum medium designed to simulate the environment in the lungs of people with CF through addition of components including mucin, free DNA and amino acids. Two different starting conditions were used for time-kill assays: a standard ∼5 × 106 cfu/mL inoculum, and a high-density inoculum in which bacteria were grown for 72 hours before addition of antibiotics. Growth detection was performed by colony enumeration and by detection of resazurin reduction.</p><p><strong>Results: </strong>There were major discrepancies between standard susceptibility results and activity in our models. Some antibiotics, including ceftazidime, showed minimal activity in all time-kill assays despite low minimal inhibitory concentrations, while others, notably tobramycin, were more active in high-density growth conditions than in standard time-kill assays.</p><p><strong>Conclusions: </strong>This work underscores the urgent need to develop more clinically relevant susceptibility testing approaches for Bcc.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2867-2876"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics of anti-TB drugs in children and adolescents with drug-resistant TB: a multicentre observational study from India.","authors":"Hemanth Kumar Agibothu Kupparam, Ira Shah, Padmapriyadarsini Chandrasekaran, Sushant Mane, Sangeeta Sharma, Bharathi Raja Thangavelu, Sudha Vilvamani, Vijayakumar Annavi, Santhana Mahalingam Mahalingam, Kannan Thiruvengadam, Poorna Gangadevi Navaneethapandian, Srushti Gandhi, Vishrutha Poojari, Zahabiya Nalwalla, Vikas Oswal, Prathiksha Giridharan, Sarath Balaji Babu, Sridhar Rathinam, Asha Frederick, Suhbangi Mankar, Shanmugam Murugaiha Jeyakumar","doi":"10.1093/jac/dkae311","DOIUrl":"10.1093/jac/dkae311","url":null,"abstract":"<p><strong>Background: </strong>Drug-resistant tuberculosis (DR-TB) is one of the challenging forms of TB to treat, not only in adults but also in children and adolescents. Further, there is a void in the treatment strategy exclusively for children due to various reasons, including paucity of pharmacokinetic (PK) data on anti-TB drugs across the globe. In this context, the present study aimed at assessing the PK of some of the anti-TB drugs used in DR-TB treatment regimens.</p><p><strong>Method: </strong>A multicentre observational study was conducted among DR-TB children and adolescents (n = 200) aged 1-18 years (median: 12 years; IQR: 9-14) treated under programmatic settings in India. Steady-state PK (intensive: n = 89; and sparse: n = 111) evaluation of moxifloxacin, levofloxacin, cycloserine, ethionamide, rifampicin, isoniazid and pyrazinamide was carried out by measuring plasma levels using HPLC methods.</p><p><strong>Results: </strong>In the study population, the frequency of achieving peak plasma concentrations ranged between 13% (for rifampicin) to 82% (for pyrazinamide), whereas the frequency of suboptimal peak concentration for pyrazinamide, cycloserine, moxifloxacin, levofloxacin and rifampicin was 15%, 19%, 29%, 41% and 74%, respectively. Further, the frequency of supratherapeutic levels among patients varied between 3% for pyrazinamide and 60% for isoniazid. In the below-12 years age category, the median plasma maximum concentration and 12 h exposure of moxifloxacin were significantly lower than that of the above-12 years category despite similar weight-adjusted dosing.</p><p><strong>Conclusions: </strong>Age significantly impacted the plasma concentration and exposure of moxifloxacin. The observed frequencies of suboptimal and supratherapeutic concentrations underscore the necessity for dose optimization and therapeutic drug monitoring in children and adolescents undergoing DR-TB treatment.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2939-2947"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142287899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Deleterious effects of a combination therapy using fluoroquinolones and tetracyclines for the treatment of Japanese spotted fever: a retrospective cohort study based on a Japanese hospital database.","authors":"Kazuhiro Itoh, Hiroshi Tsutani, Daijiro Kabata, Shigetoshi Sakabe, Yasuhiko Mitsuke, Hiromichi Iwasaki","doi":"10.1093/jac/dkae352","DOIUrl":"10.1093/jac/dkae352","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"3049-3050"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Plasmid-mediated azithromycin resistance in non-typhoidal Salmonella recovered from human infections.","authors":"","doi":"10.1093/jac/dkae362","DOIUrl":"10.1093/jac/dkae362","url":null,"abstract":"","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"3053"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142347112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An innovative population pharmacokinetic/pharmacodynamic strategy for attaining aggressive joint PK/PD target of continuous infusion ceftazidime/avibactam against KPC- and OXA-48- producing Enterobacterales and preventing resistance development in critically ill patients.","authors":"Pier Giorgio Cojutti, Manjunath P Pai, Milo Gatti, Matteo Rinaldi, Simone Ambretti, Pierluigi Viale, Federico Pea","doi":"10.1093/jac/dkae290","DOIUrl":"10.1093/jac/dkae290","url":null,"abstract":"<p><strong>Objectives: </strong>Ceftazidime/avibactam is a key antibiotic for carbapenemase-producing Enterobacterales (CPE) Gram-negative infections, but current dosing may be suboptimal to grant activity. This study explores the population pharmacokinetics/pharmacodynamics (PK/PD) of continuous infusion (CI) ceftazidime/avibactam for maximizing treatment efficacy in critically ill patients.</p><p><strong>Methods: </strong>A retrospective analysis of adult patients receiving CI ceftazidime/avibactam and therapeutic drug monitoring (TDM) of both compounds was performed. Population PK/PD modelling identified the most accurate method for estimating ceftazidime/avibactam clearance based on kidney function and Monte Carlo simulations investigated the relationship between various CI dosing regimens and aggressive joint PK/PD target attainment of ceftazidime/avibactam.</p><p><strong>Results: </strong>The European Kidney Function Consortium (EKFC) equation best described kidney function for ceftazidime/avibactam clearance. The findings challenge the current approach of only reducing the ceftazidime/avibactam dose based on kidney function by identifying dose adjustments in patients with augmented kidney function. Our CI ceftazidime/avibactam dosing strategies, adjusted by TDM, showed promise for achieving optimal aggressive joint PK/PD targets and potentially improving clinical/microbiological outcomes against KPC- and OXA-48-producing Enterobacterales. The risk of neurotoxicity associated with these strategies appears acceptable.</p><p><strong>Conclusions: </strong>This study suggests that adjusting ceftazidime/avibactam dosing regimen based solely on eCLcr might be suboptimal for critically ill patients. Higher daily doses delivered by CI and adjusted based on TDM have the potential to improve aggressive joint PK/PD target attainment and potentially clinical/microbiological outcomes. Further investigations are warranted to confirm these findings and establish optimal TDM-guided dosing strategies for ceftazidime/avibactam in clinical practice.</p>","PeriodicalId":14969,"journal":{"name":"Journal of Antimicrobial Chemotherapy","volume":" ","pages":"2801-2808"},"PeriodicalIF":3.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}